We have previously shown that endothelium-dependent vascular relaxation is abnormal in hypertensive patients. However, because the endothelial regulation of vascular tone is mediated through the release of several factors, we undertook the present investigation to determine the role of endothelium-derived nitric oxide in the abnormal endothelial function of these patients. To this purpose, we studied the forearm vasculature response to intra-arterial infusion of the endothelium-dependent vasodilator acetylcholine, and the direct smooth muscle dilator sodium nitroprusside in 11 hypertensive patients (age 46.5+9 years; 7 men and 4 women). The response to these drugs was studied before and after infusion of N-monomethyl-L-arginine (L-NMMA: an inhibitor of endothelial synthesis of endothelium-derived nitric oxide). The results were compared to similar studies performed in 10 normal controls (age 45+7 years; 7 men and 3 women). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by strain gauge plethysmography. Basal blood flow was similar in normal controls and hypertensive patients. L-NMMA produced a significantly greater decrease in blood flow in controls that in patients. As shown previously, the response to acetylcholine was reduced in patients compared to controls; however, the response to sodium nitroprusside was similar in the two groups. L-NMMA blunted the vasodilator response to acetylcholine in controls; however, this drug did not significantly modify the response to acetylcholine in hypertensive patients. Thus, the vascular effects of inhibition of endothelium-derived nitric oxide are attenuated in patients with essential hypertension. These findings are compatible with the concept that endothelial release of nitric oxide is abnormal in hypertensive patients and may account for the impaired endothelium- dependent vascular relaxation.